Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Cannabis has long been used for fibre (hemp), for medicinal purposes, and as a recreational drug.
Cannabinoid is a generic term for phytocannabinoids, endocannabinoids, and synthetic cannabinoids. Phytocannabinoids are the natural compounds found in the Cannabis plants. More than 60 cannabinoids have been isolated from Cannabis plants with tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) being the most prevalent natural cannabinoids. THC is the primary psychoactive component of the plant and has been used to treat a wide range of medical conditions. More specifically, THC binds to specific receptors in the brain called cannabinoid receptors and, in doing so, causes some pain reduction, may reduce aggression, can stimulate appetite, and helps reduce nausea.
CBD is not considered to be psychoactive but has been reported to relieve convulsions, inflammation, anxiety, and nausea. CBN is considered to be mildly psychoactive and is the primary product of THC degradation; thus, its concentration increases during storage as well as with exposure to light, heat, and air.
Endocannabinoids activate the cannabinoid receptors and are found in nervous and immune systems, while synthetic cannabinoids are a structurally diverse group of substances also capable of binding to cannabinoid receptors. Classical cannabinoids are considered to be a chemical class of synthetic cannabinoids that are structurally related to THC.
FIG. 1 from U.S. Pat. No. 7,449,589, incorporated herein by reference, shows various cannabinoid compounds including THC, CBD, and CBN. THC reportedly has at least eight individual isomers of which (−)-Δ9-trans-tetrahydrocannabinol ((−)-Δ9-trans-THC) is the main and most active isomer. Although Δ8-tetrahydrocannabinol has similar activity as (−)-Δ9-trans-THC, it is only approximately 75% as potent and also tends to degrade to other compounds including CBN. Several pharmaceutical products exist which contain either phytocannabinoids (natural) or synthetic cannabinoids. For example, dronabinol (Marinol®) is the International Nonproprietary Name (INN) for an encapsulated THC product which has been used therapeutically as an appetite stimulant, antiemetic, and analgesic, either as an inhalant or as an oral drug. Also, nabilone (Cesamet®) is a synthetic analog of dronabinol (Marinol®), while Sativex is a cannabinoid extract oral spray containing THC and other cannabinoids which is used to treat neuropathic pain and spasticity. Further, rimonabant (marketed under various tradenames) is a selective cannabinoid receptor antagonist used as an anti-obesity drug and as a smoking cessation. Several other cannabinoid-containing products exist and others will likely soon be marketed.
Thus, considering the therapeutic effect of compositions containing cannabinoids, especially (−)-Δ9-trans-THC, there is a continuing need for improving existing cannabinoid-containing products as well as a need for new products containing cannabinoids, especially in the pharmaceutical field.
WO 2006/063109, incorporated herein by reference, discloses an encapsulated THC composition including (−)-Δ9-trans-THC purportedly having improved stability. The WO '109 application emphasizes that stability can be improved by including bases (e.g., amines) in the formulation. In addition, the stability of the compositions of the WO '109 application is best preserved by storing the compositions in a sealed container, such as in a capsule, and under refrigerated conditions. More specifically, the WO '109 application asserts that one embodiment of the invention described therein overcomes the deficiencies of prior art oral dosage forms containing (−)-Δ9-trans-THC by utilizing hard gelatin capsules, instead of soft gelatin capsules. As stated in the application, unlike soft gelatin capsules, hard gelatin capsules do not contain glycerol, a major cause of instability for the active (−)-Δ9-trans-THC pharmaceutical ingredient. The WO '109 application purports to provide a stable product, such as one that does not degrade to an unacceptable extent during the desired shelf-life of the dosage form.